**10. miRNA regulation in goat immune system**

Recent literature cites of the immune cells that are communicated through from one cell to other by transferring regulatory RNAs, microRNAs in particular. Many studies pin point that some sort of functional, regulatory extracellular RNAs plays a key role in cell-to-cell communication in various cellular processes [125]. MicroRNAs (miRNAs) are group of short RNA non coding sequences that are highly conserved between different eukaryotic species [126]. These are ~19–28 nucleotides long sequences that regulate(s) gene expression [127, 128]. miRNAs are particularly important in the cellular function that show time dependent responses [129]. miRNA literature show that they partake a mesmerizing role in both immune system and as an immune system [130]. These small RNAs lead to vertebrates transcriptional silences like a rheostat that act to fine tune (rather than complete shut-off) of translational products. The miRNA targeting could result in 3-fold decrease of mRNA transcripts [131]. In many studies, till now, more than 60% miRNA expression profiles are developed and tested in variety of tissues from livestock. These profiling post transcriptional regulate gene expression in several cellular processes such as differentiation, and transformation processes in cell cycle through signal transduction [127, 132]. miRNA molecules could broadly act as regulators on shorter time scale on protein transcriptional repressors that effect inflammation. They can also show quicker results without engaging translational or translocational machinery within the nucleus and controlling regulators. One example to this is the miR 155 regulation [129, 133]. Together with these options opens up many avenues that provide novel and exciting products in therapeutic as well as in clinical use, specifically for immunity and inflammation Today miRNA functionality can be dissected in leukocyte differentiation, innate signaling, and TH cell biology [132]. *In-silico* studies using various tools on miRNAs on computation or experiments gathered about 35 Helminthes (11 Trematodes, 8 Cestodes, and 16 Nematodes, and two plant origin parasitic Nematodes). These analysis show that greater than 620

**173**

*Goat Immunity to Helminthes*

*DOI: http://dx.doi.org/10.5772/intechopen.91189*

124a in the presence of EVs of *C. sinensis* [133, 139].

**10.1 miRNA regulation of T cells**

plus pre-miRNAs that are listed in miRBase of parasitic origin. Interestingly, the first miRNA was discovered in *C. elegans*, a nematode [133]. All known parasite miRNA database entries are analogous to miR database. The emerging, neglected disease of *Schistosoma*, a trematode, is one of the iRNA models in the whole family [134]. The miR database showed that there are 79 and 225 mature miRNAs associated to *S. japonicum* and *S. mansoni* respectively. These findings indicates that not only large number of variations do occur within the helminthes, but male and female worms also show differences. This also give insight to the role in morphogenesis, development and reproduction [135]. A similar picture arises from Next Generation Sequencing (NGS) and bioinformatic analysis and experimentation with stem-loop qRT-PCR identifies 13 species specific miRs in two species *Fasciola hepatica* and *F. gigantica* [134]. Studies on infection, more than 130 miRNA (analogy to other parasitic miRNA), are seen to flocculate in expression profile [135, 136]. It is shown at many instances that miR 155, miR 223, miR 146 are negative, suppressors of cytokine in a regulatory loop. In other studies, miR 155 is also interactive to transcriptional factor cMaf and tempers with TH 2 within the CD 4 group. In another analogy to a mouse model, same miRNA 34c, miR, miR199, miR 134, miR 223, and miR 214 are shown to effect 220 miRNA parasitic immune response silhouette [133, 137]. The powerful approaches of bioinformatics extrapolations along with stemloop real-time PCR analysis on the *C. sinensis* showed that there are a total of 62,512 conserved miRNA sequences which includes six novel identified miRNA [138]. Pak and coworkers [135] demonstrated that there is an upregulation miR 16-2, miR 93, miR 95, miR 153, miR195, miR 199a-3p, and silences with miR let7a, let 7i, and miR

As a critical role of miRNA post transcriptional regulation in transformation within immune cells show that these tiny molecules can reduce the expression of various genes by 3 orders of magnitude during maturation [140]. Studies showed that different miRNAs are involved in the thymocytes development by Dicer or Drosha knockouts experiments. Obstruction in the process consequential drop of mature Tαβ and natural killer T (NKT) cells [141]. In animals' helminthic studies, absence or presence of miR 155, showed that it can effect TH 2 differentiation involving apoptotic processes [131]. miRNA machinery knockout experiments demonstrate that some of the miRNA are of absolute requirement for Thymic development and peripheral function of nTreg cells. However, dicer knockout of Fox P3 cells consequences to nTreg cells without oppressive role. Treg cells can also transform into T follicular helper cells that resulted in loss of immunomodulation and B cell activation in this scenario miR 155 is a regulator of nTreg cells. It should be remembered that miR 155 is expressed in all adaptive immune cells [142]. The expression and formation of active miR 181a is found to be tightly regulated intrathymic T cell development. The activities modulates the T cell antigen receptor (TCR) retort the down regulation through phosphatases which plays pivotal role in reducing TCR cell signaling. Thus the activities of miR 181a acts to modulates of TCR sensitivity towards T cell development in the lymphoid organ [131]. Blockage with antagomir (oligonucleotide) to miR 126 reduces the differentiation of TH 2 which are linked to helminthic pathogenesis during innate immune system activation. During this impasse, TH 17 cells regulate another miR 326 within their reach by up regulation [143]. These cells are differentiated and regulated by cytokine IL 23 [144]. It is shown that miR 17 polarizes then TH 2 cells, required in type 2 immune response to helminthes infection [141]. Mature TH cells are further influenced by miR 182 in response to IL 2 cytokine synthesis. This regulation is

## *Goat Immunity to Helminthes DOI: http://dx.doi.org/10.5772/intechopen.91189*

*Goats (Capra) - From Ancient to Modern*

ment activities [124] (**Figure 9**).

**10. miRNA regulation in goat immune system**

Recent literature cites of the immune cells that are communicated through from one cell to other by transferring regulatory RNAs, microRNAs in particular. Many studies pin point that some sort of functional, regulatory extracellular RNAs plays a key role in cell-to-cell communication in various cellular processes [125]. MicroRNAs (miRNAs) are group of short RNA non coding sequences that are highly conserved between different eukaryotic species [126]. These are ~19–28 nucleotides long sequences that regulate(s) gene expression [127, 128]. miRNAs are particularly important in the cellular function that show time dependent responses [129].

miRNA literature show that they partake a mesmerizing role in both immune system and as an immune system [130]. These small RNAs lead to vertebrates transcriptional silences like a rheostat that act to fine tune (rather than complete shut-off) of translational products. The miRNA targeting could result in 3-fold decrease of mRNA transcripts [131]. In many studies, till now, more than 60% miRNA expression profiles are developed and tested in variety of tissues from livestock. These profiling post transcriptional regulate gene expression in several cellular processes such as differentiation, and transformation processes in cell cycle through signal transduction [127, 132]. miRNA molecules could broadly act as regulators on shorter time scale on protein transcriptional repressors that effect inflammation. They can also show quicker results without engaging translational or translocational machinery within the nucleus and controlling regulators. One example to this is the miR 155 regulation [129, 133]. Together with these options opens up many avenues that provide novel and exciting products in therapeutic as well as in clinical use, specifically for immunity and inflammation Today miRNA functionality can be dissected in leukocyte differentiation, innate signaling, and TH cell biology [132]. *In-silico* studies using various tools on miRNAs on computation or experiments gathered about 35 Helminthes (11 Trematodes, 8 Cestodes, and 16 Nematodes, and two plant origin parasitic Nematodes). These analysis show that greater than 620

which is produced in response to any infection which later isotopically switch to Ig E functions [117]. Locally generated IgG1 is also detected after arthritis encephalitis (CAE) virus infection in the synovial fluid [118]. Very few work has been done for caprine IgM concentrations and activities. All the ruminant species observe little structural and functional differences [119]. Caprine IgA, on the other hand, is detectable from serum, colostrum, milk, saliva, and urine. IgA is the primary immunoglobulin present in mucosal surfaces. The secretory element to IgA could be found in either free-state or bound to IgA molecule. The serum very small amount of IgA is linked to secretory component [120]. Goat mucosal immune system produces sIgA by antibody producing cells differentiated from activated B cells. Immunoglobulin class switch do occur from IgA in gut-associated lymphoid (GAL) in Peyer's patches, MLNs, and ILFs within the lamina propria [28, 121]. The humoral immunoglobulin isotype switch occurs through intestinal pDCs, T cell-independent manner and B cell-activating factors (BAFFs) and A proliferation-inducing ligand (APRIL) proliferation inducing ligand [73]. Like in all ruminants, including goats, IgE typically associated to its biologic activities. Today IgE is accepted as useful marker in identifying different phases of parasites and parasite resistance. Nucleic acid sequencing in caprine IgE DNA is part of the overall effort [110, 122]. Goat's complement system is provided with limited concentrations [123]. Dynamic studies showed that in less than 6 month old young and adult indicate significant hemolytic, conglutinating, and bactericidal comple-

**172**

plus pre-miRNAs that are listed in miRBase of parasitic origin. Interestingly, the first miRNA was discovered in *C. elegans*, a nematode [133]. All known parasite miRNA database entries are analogous to miR database. The emerging, neglected disease of *Schistosoma*, a trematode, is one of the iRNA models in the whole family [134]. The miR database showed that there are 79 and 225 mature miRNAs associated to *S. japonicum* and *S. mansoni* respectively. These findings indicates that not only large number of variations do occur within the helminthes, but male and female worms also show differences. This also give insight to the role in morphogenesis, development and reproduction [135]. A similar picture arises from Next Generation Sequencing (NGS) and bioinformatic analysis and experimentation with stem-loop qRT-PCR identifies 13 species specific miRs in two species *Fasciola hepatica* and *F. gigantica* [134]. Studies on infection, more than 130 miRNA (analogy to other parasitic miRNA), are seen to flocculate in expression profile [135, 136]. It is shown at many instances that miR 155, miR 223, miR 146 are negative, suppressors of cytokine in a regulatory loop. In other studies, miR 155 is also interactive to transcriptional factor cMaf and tempers with TH 2 within the CD 4 group. In another analogy to a mouse model, same miRNA 34c, miR, miR199, miR 134, miR 223, and miR 214 are shown to effect 220 miRNA parasitic immune response silhouette [133, 137]. The powerful approaches of bioinformatics extrapolations along with stemloop real-time PCR analysis on the *C. sinensis* showed that there are a total of 62,512 conserved miRNA sequences which includes six novel identified miRNA [138]. Pak and coworkers [135] demonstrated that there is an upregulation miR 16-2, miR 93, miR 95, miR 153, miR195, miR 199a-3p, and silences with miR let7a, let 7i, and miR 124a in the presence of EVs of *C. sinensis* [133, 139].
